Known antiviral agents comprising glycosides of sulfated oligosaccharides include EP 0497988, EP 0506048 and EP 0532026 which have been each provided by the present inventors. It has been clarified that when a sulfated oligosaccharide is formulated into a glycoside, its antiviral activity is increased one order over the activity of the non-glycoside compound. When orally administered, however, these sulfated compounds, which have never been acylated at the sugar hydroxyl groups, are poor in long-lasting action in the blood.
Although antiviral agents comprising sulfated polysaccharide alkyl ethers or alkyl esters have been disclosed in JP-A-3-43401, neither any aromatic glycosides, tocopherol glycosides nor aromatic esterification are described therein (the term "JP-A" as used herein means an "unexamined published Japanese patent application").
Although U.S. Pat. No. 4,840,815 has disclosed esterified alkyl glycosides comprising oligosaccharides, these compounds are not sulfated but only esterified. Further, JP-A-4-264102 has disclosed compounds wherein the sugar hydroxyl groups of galactomannane are substituted with aliphatic, aromatic/aliphatic or aromatic ethers or aromatic esters. However, these compounds are neither glycosides nor sulfated compounds, different from the compounds of the present invention.
U.S. Pat. No. 4,597,770 has disclosed sulfates of alkyl glycoside alkyl ethers comprising mono- to deca-saccharides as a coal-slurrying agent. However, the detailed structures of these compounds are not clearly given therein and the sugar hydroxyl groups of these compounds have never been acylated. Thus the compounds disclosed in this patent completely differ from the compounds according to the present invention.
Furthermore, U.S. Pat. No. 4,761,401 has disclosed diglycoside sulfates containing uronic acid. However, these compounds also differ from the compounds according to the present invention, since their sugar chains consist of two saccharides and these compounds contain uronic acid. Although U.S. Pat. No. 3,478,016 has disclosed sulfates of cellulose esters and cellulose ethers, these compounds are not intended to be used as an antiviral agent and, further, their structures have not been clearly given in this patent.
As described above in brief, there has been known no oligoglycoside the sugar hydroxyl group of which has been acylated and sulfated.
In recent years, there has been reported that sulfated polysaccharides are effective as an antiviral agent, in particular, an anti-HIV agent [refer to U.S. Pat. No. 4,783,446 and M. Baba et al., Journal of Acquired Immune Deficiency Syndrome, 3, 493-499 (1990)]. However, each of these sulfated polysaccharides has no glycoside structure and a large molecular weight of several ten thousands or above, which causes various problems such as having poor absorption characteristics in vivo, being hardly usable in oral administration, having a high anticoagulant activity and frequently metabolising within 1 hour after the administration due to a poor long-lasting action in the blood. In addition, AZT (3'-azido-3'-deoxythymidine), which has been widely used as an anti-AIDS agent, has serious side effects. Accordingly, it has been urgently required to develop a novel drug with a low toxicity.